Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis.

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis.

Modern Look at Transverse Myelitis and Inflammatory Myelopathy: Epidemiology of the National Veterans Health Administration Population.

Background And Objectives: To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA).

Methods: This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria.

Ultrahigh-b diffusion-weighted imaging for quantitative evaluation of myelination in shiverer mouse spinal cord.

Purpose: To perform a quantitative evaluation of myelination on WT and myelin-deficient (shiverer) mouse spinal cords using ultrahigh-b diffusion-weighted imaging (UHb-DWI).

Methods: UHb-DWI of ex vivo on spinal cord specimens of two shiverer (C3HeB/FeJ-shiverer, homozygous genotype for MbP ) and six WT (Black Six, C3HeB/FeJ) mice were acquired using 3D multishot diffusion-weighted stimulated-echo EPI, a homemade RF coil, and a small-bore 7T MRI system. Imaging was performed in transaxial plane with 75 × 75 μm in-plane resolution, 1-mm-slice thickness, and radial DWI using b = 42,890 s/mm .

High-b diffusivity of MS lesions in cervical spinal cord using ultrahigh-b DWI (UHb-DWI).

Purpose: The purpose of this study was to investigate UHb-rDWI signal in white matter tracts of the cervical spinal cord (CSC) and compare quantitative values between healthy control WM with both MS NAWM and MS WM lesions.

Methods: UHb-rDWI experiments were performed on (a) 7 MS patients with recently active or chronic lesions in CSC and on (b) 7 healthy control of similar age range and gender distribution to MS subjects. All MRI data were acquired using clinical 3T MRI system.

Improvement of Comorbid Psoriasis in Patients With MS Treated With Natalizumab.

Objective: To present observations on administration of natalizumab to 18 patients with the comorbid MS and psoriasis, who represented a full subset of patients with such comorbidity within the patient records available.

Methods: A retrospective analysis of patient records was performed. Patient histories were gathered and included date of diagnosis of MS and psoriasis, MS disease-modifying therapies (DMTs), Expanded Disability Status Scale (EDSS), reason for DMT switch, and effects on MS and psoriasis status.

Treatment-responsive primary autoimmune cerebellar ataxia in a patient with IgG and IgM anticerebellar antibodies.

Background And Purpose: Primary autoimmune cerebellar ataxia (PACA) in the absence of another triggering disease represents an emerging category of neurological illness. We report such a case whose ataxia was markedly responsive to plasma exchange. We analyzed patient serum for the presence of IgM or IgG anticerebellar neuronal antibodies.

Genetic deletion of ADP-activated P2Y receptor ameliorates lithium-induced nephrogenic diabetes insipidus in mice.

Aim: Therapeutic use of lithium in bipolar disorder is limited by the development of nephrogenic diabetes insipidus (NDI). We reported that pharmacological blockade of P2Y receptor (R) with clopidogrel or prasugrel significantly ameliorated lithium-induced NDI in rodents. Using mice genetically lacking P2Y -R we evaluated whether the observed amelioration is mediated through P2Y -R METHODS: P2ry12 mouse line (C57/BL6) was rederived from cryopreserved embryos of the knockout (KO) mice generated by Deltagen Inc.

Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

Previously, we localized ADP-activated P2Y receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists.

Voltage-gated calcium channel autoimmune cerebellar degeneration: Case and study of cytotoxicity.

Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures.

Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies.

Results: A 53-year-old man developed progressive incoordination with ataxic speech.

Retinal nerve fiber layer sector-specific compromise in relapsing and remitting multiple sclerosis.

Objective: To evaluate quadrant and sector retinal nerve fiber layer (RNFL) thickness and total macular volume (TMV) in relapsing-remitting multiple sclerosis (RR-MS) patients.

Methods: Optical coherence tomography measures of RNFL and TMV were studied in 321 eyes without prior optic neuritis (ON) (MS unaffected), 151 eyes with prior ON (MS affected), and 148 healthy control eyes.

Results: Mean RNFL thickness was significantly lower in the MS affected and MS unaffected groups relative to the control group ( < 0.

Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice.

Lithium (Li) administration causes deranged expression and function of renal aquaporins and sodium channels/transporters resulting in nephrogenic diabetes insipidus (NDI). Extracellular nucleotides (ATP/ADP/UTP), via P2 receptors, regulate these transport functions. We tested whether clopidogrel bisulfate (CLPD), an antagonist of ADP-activated P2Y(12) receptor, would affect Li-induced alterations in renal aquaporins and sodium channels/transporters.

The role of the prostaglandin E2 receptors in vulnerability of oligodendrocyte precursor cells to death.

Background: Activity of cyclooxygenase 2 (COX-2) in mouse oligodendrocyte precursor cells (OPCs) modulates vulnerability to excitotoxic challenge. The mechanism by which COX-2 renders OPCs more sensitive to excitotoxicity is not known. In the present study, we examined the hypothesis that OPC excitotoxic death is augmented by COX-2-generated prostaglandin E2 (PGE2) acting on specific prostanoid receptors which could contribute to OPC death.

Anti-Yo antibody uptake and interaction with its intracellular target antigen causes Purkinje cell death in rat cerebellar slice cultures: a possible mechanism for paraneoplastic cerebellar degeneration in humans with gynecological or breast cancers.

Anti-Yo antibodies are immunoglobulin G (IgG) autoantibodies reactive with a 62 kDa Purkinje cell cytoplasmic protein. These antibodies are closely associated with paraneoplastic cerebellar degeneration in the setting of gynecological and breast malignancies. We have previously demonstrated that incubation of rat cerebellar slice cultures with patient sera and cerebrospinal fluid containing anti-Yo antibodies resulted in Purkinje cell death.

P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells.

Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures.

Background: Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction.

Advances in the management of neurogenic detrusor overactivity in multiple sclerosis.

Bladder dysfunction in multiple sclerosis (MS) can be socially disabling, have negative psychological and economic consequences, and impair patients' quality of life. Knowledge of the functional anatomy and physiology of the urinary tract is essential to understand the symptoms associated with central nervous system lesions and the pharmacotherapies used to treat them. Treatments for neurogenic detrusor overactivity (NDO) have consisted mainly of administration of anticholinergic drugs, which have been shown to provide suboptimal clinical benefits and be poorly tolerated.

Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis.

The polyphenol compound resveratrol is reported to have multiple functions, including neuroprotection, and no major adverse effects have been reported. Although the neuroprotective effects have been associated with sirtuin 1 activation by resveratrol, the mechanisms by which resveratrol exerts such functions are a matter of controversy. We examined whether resveratrol can be neuroprotective in two models of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD).

Optical coherence tomography as a biomarker in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that leads to axonal dysfunction and neuronal loss and often presents optic neuritis (ON). Decreased thickness of the retinal nerve fiber layer (RNFL) is a classic finding on ophthalmoscopic examination of patients with MS and especially noted in those patients with a history of ON. The thickness of the RNFL can be measured by a non-invasive technique, optical coherence tomography (OCT).

Vitamin D as a clinical biomarker in multiple sclerosis.

Introduction: Vitamin D has attracted a lot of attention in relation to multiple sclerosis (MS) and many other disorders; however, the evidence for a major role(s) for vitamin D in MS is compelling and multifactorial involving results from epidemiology, immunology, genetics, biochemistry and translational medicine.

Areas Covered: Multiple studies that illustrate that insufficient levels of vitamin D not only contribute to the risk of getting MS but may also worsen disease progression for MS patients are discussed. Genetic evidence also implicates vitamin D as being important in MS since individuals are at greater risk of getting MS if they harbor a mutation in a gene responsible for vitamin D synthesis (25-hydroxylase).

Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria.

Clinical biomarkers in multiple sclerosis.

Introduction: The search for meaningful biomarkers for multiple sclerosis (MS) has intensified in the past 5 years. Substantial progress is continuing in this multifaceted field. Recent advances offer important potential for new clinical tools to assist in diagnosis, detection of disease-associated conditions or cofactors, assessment of treatment efficacy and determination of disease progression.